{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T23:02:53Z","timestamp":1769209373219,"version":"3.49.0"},"reference-count":66,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["11901013"],"award-info":[{"award-number":["11901013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["1204031"],"award-info":[{"award-number":["1204031"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["BMU2021RCZX023"],"award-info":[{"award-number":["BMU2021RCZX023"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"PKU-Baidu Fund","award":["2020BD029"],"award-info":[{"award-number":["2020BD029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Objective: to evaluate the risk of treatment-related adverse events of different severity and different system with PD-1 or PD-L1 inhibitors. Methods: randomized controlled trials (RCTs) that using PD-1\/PD-L1 for cancer treatment were searched in the PubMed, Embase, Cochrane Library, and Web of Science from 1 January 2019 to 31 May 2021. Adverse events data were extracted from clinical trials website or original article by two authors separately. Meta-analysis was used to determine risk ratio (RR) and 95% confidence interval (95% CI) of adverse events in PD-1\/PD-L1 inhibitors groups compared to that of control groups. Subgroup analyses were also performed. Results: a total of 5,807 studies were initially identified and after exclusion, 41 studies were included in meta-analysis. All the trials were international multicenter, randomized, phase II\/III clinical trials, with the median follow-up of 27.5 months on average. Analysis of all grade adverse events showed that PD-1\/PD-L1 inhibitors treatment significantly increased the risk of immune-related adverse events, including pruritus (RR: 2.34, 95% CI: 1.85\u20132.96), rash (RR: 1.53, 95% CI: 1.25\u20131.87), ALT elevation (RR 1.54, 95% CI 1.23\u20131.92), AST elevation (AST: RR 1.49, 95% CI 1.20\u20131.85), hepatitis (RR: 3.54, 95% CI: 1.96\u20136.38) and hypothyroid (RR: 5.29, 95% CI: 4.00\u20136.99) compared with that of control group. Besides that, PD-1\/PD-L1 inhibitors were associated with higher risk of adverse events related to respiratory system including cough (RR: 1.33, 95% CI: 1.21\u20131.48), dyspnea (RR:1.23, 95% CI: 1.12\u20131.35) and chest pain (RR: 1.26, 95% CI: 1.07\u20131.47) compared with that of control groups in our meta-analysis and the dyspnea was taken high risk both in all grade and grade 3 or higher (RR: 1.55, 95% CI: 1.13\u20132.12). The risk of arthralgia was increased with PD-1\/PD-L1 inhibitors (RR: 1.27, 95% CI: 1.10\u20131.47). Although the risk of myalgia was similar with PD-1\/PD-L1 inhibitors and control groups, under subgroup analysis, PD-1\/PD-L1 inhibitors decreased the risk of myalgia (RR: 0.56, 95% CI: 0.45\u20130.70) compared with that of chemotherapy. Conclusions: our results provide clear evidence that the risk of treatment-related adverse events in PD-1 or PD-L1 varies widely in different system. In particular, when using PD-1\/PD-L1 inhibitors for oncology treatment, besides the common immune-related adverse events like pruritus, rash, hepatitis, and hypothyroid, the respiratory disorders and musculoskeletal disorders, such as cough, dyspnea, arthralgia, and myalgia, should also be taken into consideration.<\/jats:p>","DOI":"10.3390\/life11111277","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T01:43:22Z","timestamp":1638323002000},"page":"1277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Treatment-Related Adverse Events with PD-1 or PD-L1 Inhibitors: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"11","author":[{"given":"Yixi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biostatistics, School of Public Health, Peking University, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"La","sequence":"additional","affiliation":[{"name":"School of Public Health, Peking University, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3500-0820","authenticated-orcid":false,"given":"Baosheng","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, Peking University, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangchun","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1080\/21645515.2019.1571892","article-title":"PD-1 and PD-L1 in cancer immunotherapy: Clinical implications and future considerations","volume":"15","author":"Jiang","year":"2019","journal-title":"Hum. 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